Chopra Arvind
National Center for Biotechnology Information, NLM, Bethesda, MD 20894
A bifunctional chelating agent (BFC) such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is often used to link a radionuclide with a monoclonal antibody (mAb) for the targeted imaging or radioimmunotherapy of cancers (1). However, a major limitation of using BFCs is that harsh reaction conditions such as high temperatures are required to facilitate the formation of the radionuclide-BFC complex (2). In addition, these complexes are not very stable . Ferreira et al. developed two BFCs, 1-oxa-4,7,10-triazacyclododecane--5-(4-nitrobenzyl)-4,7,10-triacetic acid (-NO(2)-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene--4-(4-nitrobenzyl)-3,6,9-triacetic acid (-NO(2)-Bn-PCTA), and showed that these chelators produced stable radiolabeled complexes with Cu under mild conditions ([Cu]-Oxo-DO3A and [Cu]-PCTA) (3). A preliminary biodistribution study in mice showed that, compared with [Cu]-DOTA, there was a lower accumulation of radioactivity in the liver with [Cu]-Oxo-DO3A and [Cu]-PCTA. It was also observed that clearance of the label from the kidneys of the animals was faster with [Cu]-PCTA than with either [Cu]-Oxo-DO3A or [Cu]-DOTA (3). Trastuzumab is a monoclonal antibody (mAb) that targets the HER2/ receptor, which is overexpressed in several types of cancer and is indicative of a poor prognosis for the patient (4). This mAb was approved by the United States Food and Drug Administration for the treatment of various cancers, and its radiolabeled form has been evaluated for the detection and radioimmunotherapy of the disease (5). Because the characteristics and applications of trastuzumab are well understood, Ferreira et al. investigated and compared the and properties of the Cu-labeled PCTA, Oxo-DO3A, and DOTA conjugates of this mAb (2).
双功能螯合剂（BFC），如1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA），常被用于将放射性核素与单克隆抗体（mAb）连接，以用于癌症的靶向成像或放射免疫治疗（1）。然而，使用BFC的一个主要限制是需要高温等苛刻的反应条件来促进放射性核素-BFC复合物的形成（2）。此外，这些复合物不是很稳定。费雷拉等人开发了两种BFC，即1-氧杂-4,7,10-三氮杂环十二烷-5-(4-硝基苄基)-4,7,10-三乙酸（-NO(2)-Bn-Oxo-DO3A）和3,6,9,15-四氮杂双环[9.3.1]十五碳-1(15),11,13-三烯-4-(4-硝基苄基)-3,6,9-三乙酸（-NO(2)-Bn-PCTA），并表明这些螯合剂在温和条件下与铜形成了稳定的放射性标记复合物（[Cu]-Oxo-DO3A和[Cu]-PCTA）（3）。一项在小鼠身上进行的初步生物分布研究表明，与[Cu]-DOTA相比，[Cu]-Oxo-DO3A和[Cu]-PCTA在肝脏中的放射性积累较低。还观察到，与[Cu]-Oxo-DO3A或[Cu]-DOTA相比，[Cu]-PCTA使动物肾脏中标记物清除得更快（3）。曲妥珠单抗是一种靶向HER2/受体的单克隆抗体（mAb），该受体在几种癌症中过度表达，表明患者预后不良（4）。这种mAb已被美国食品药品监督管理局批准用于治疗各种癌症，其放射性标记形式已被评估用于该疾病的检测和放射免疫治疗（5）。由于曲妥珠单抗的特性和应用已为人熟知，费雷拉等人研究并比较了该mAb的铜标记PCTA、Oxo-DO3A和DOTA缀合物的特性（2）。
